T Byrne, J Cooke, E McNeela, P Bambrick, R P Murphy, M Harrison
{"title":"Circulating Angiogenic and Senescent T Lymphocytes in Ageing and Frailty.","authors":"T Byrne, J Cooke, E McNeela, P Bambrick, R P Murphy, M Harrison","doi":"10.14283/jfa.2024.38","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>There is a need to identify vascular and geroscience-relevant markers and mediators that can physiologically link ageing to vascular disease. There is evidence of specific T cell subsets, all influenced by age, that exert positive and negative effects on vascular health. CD31+, termed angiogenic T cells, have been linked to vascular repair whereas CD28null, termed senescent T cells, display pro-inflammatory and cytotoxic effector functions.</p><p><strong>Objective: </strong>This study sought to determine the combined influence of increasing age and frailty status on these circulating CD31+ and CD28null T cell subsets.</p><p><strong>Methods: </strong>This cross-sectional study recruited four different cohorts of men and women; young (20-30 years, n=22), older (65-75 years, n=17), robust non-frail (76+ years, n=17), and frail (76+ years, n=15) adults. Frailty was determined using the Fried Frailty method. T cell subsets were determined by whole blood flow cytometry based on the expression of CD3, CD4, CD8, CD31 and CD28. Cognitive impairment (CI) was measured via the Montreal Cognitive Assessment test.</p><p><strong>Results: </strong>Whether expressed as circulating counts or as a % of total T cells, there was a progressive decrease (p<0.05) in CD31+ T cells with increasing age but paradoxically higher values (p<0.05) in the frail compared to the robust non-frail group. These changes were similar in the CD4+ and CD8+ fractions. CD28null T cells were considerably higher (p<0.05) in the frail compared to the robust non-frail group, including in the CD8+ (47% vs 29%, p<0.05) and CD4+ (4% vs 1%, p<0.05) fractions. CD28null T cell percentage was also higher (p<0.05) in those with moderate CI compared to mild CI and normal function.</p><p><strong>Conclusion: </strong>CD8+CD28null T cells are considerably elevated in frailty and with cognitive impairment and may serve as a useful target for intervention. Currently, the utility of CD31+ T cells as an ageing biomarker may be confined to healthy ageing cohorts.</p>","PeriodicalId":51629,"journal":{"name":"Journal of Frailty & Aging","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Frailty & Aging","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.14283/jfa.2024.38","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: There is a need to identify vascular and geroscience-relevant markers and mediators that can physiologically link ageing to vascular disease. There is evidence of specific T cell subsets, all influenced by age, that exert positive and negative effects on vascular health. CD31+, termed angiogenic T cells, have been linked to vascular repair whereas CD28null, termed senescent T cells, display pro-inflammatory and cytotoxic effector functions.
Objective: This study sought to determine the combined influence of increasing age and frailty status on these circulating CD31+ and CD28null T cell subsets.
Methods: This cross-sectional study recruited four different cohorts of men and women; young (20-30 years, n=22), older (65-75 years, n=17), robust non-frail (76+ years, n=17), and frail (76+ years, n=15) adults. Frailty was determined using the Fried Frailty method. T cell subsets were determined by whole blood flow cytometry based on the expression of CD3, CD4, CD8, CD31 and CD28. Cognitive impairment (CI) was measured via the Montreal Cognitive Assessment test.
Results: Whether expressed as circulating counts or as a % of total T cells, there was a progressive decrease (p<0.05) in CD31+ T cells with increasing age but paradoxically higher values (p<0.05) in the frail compared to the robust non-frail group. These changes were similar in the CD4+ and CD8+ fractions. CD28null T cells were considerably higher (p<0.05) in the frail compared to the robust non-frail group, including in the CD8+ (47% vs 29%, p<0.05) and CD4+ (4% vs 1%, p<0.05) fractions. CD28null T cell percentage was also higher (p<0.05) in those with moderate CI compared to mild CI and normal function.
Conclusion: CD8+CD28null T cells are considerably elevated in frailty and with cognitive impairment and may serve as a useful target for intervention. Currently, the utility of CD31+ T cells as an ageing biomarker may be confined to healthy ageing cohorts.
期刊介绍:
The Journal of Frailty & Aging is a peer-reviewed international journal aimed at presenting articles that are related to research in the area of aging and age-related (sub)clinical conditions. In particular, the journal publishes high-quality papers describing and discussing social, biological, and clinical features underlying the onset and development of frailty in older persons. The Journal of Frailty & Aging is composed by five different sections: - Biology of frailty and aging In this section, the journal presents reports from preclinical studies and experiences focused at identifying, describing, and understanding the subclinical pathophysiological mechanisms at the basis of frailty and aging. - Physical frailty and age-related body composition modifications Studies exploring the physical and functional components of frailty are contained in this section. Moreover, since body composition plays a major role in determining physical frailty and, at the same time, represents the most evident feature of the aging process, special attention is given to studies focused on sarcopenia and obesity at older age. - Neurosciences of frailty and aging The section presents results from studies exploring the cognitive and neurological aspects of frailty and age-related conditions. In particular, papers on neurodegenerative conditions of advanced age are welcomed. - Frailty and aging in clinical practice and public health This journal’s section is devoted at presenting studies on clinical issues of frailty and age-related conditions. This multidisciplinary section particularly welcomes reports from clinicians coming from different backgrounds and specialties dealing with the heterogeneous clinical manifestations of advanced age. Moreover, this part of the journal also contains reports on frailty- and age-related social and public health issues. - Clinical trials and therapeutics This final section contains all the manuscripts presenting data on (pharmacological and non-pharmacological) interventions aimed at preventing, delaying, or treating frailty and age-related conditions.The Journal of Frailty & Aging is a quarterly publication of original papers, review articles, case reports, controversies, letters to the Editor, and book reviews. Manuscripts will be evaluated by the editorial staff and, if suitable, by expert reviewers assigned by the editors. The journal particularly welcomes papers by researchers from different backgrounds and specialities who may want to share their views and experiences on the common themes of frailty and aging.The abstracting and indexing of the Journal of Frailty & Aging is covered by MEDLINE (approval by the National Library of Medicine in February 2016).